{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Koo BK"],"funding":["National Institute of Neurological Disorders and Stroke","NINDS NIH HHS"],"pagination":["619279"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7930385"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14"],"pubmed_abstract":["Wild-type human SOD1 forms a highly conserved intra-molecular disulfide bond between C57-C146, and in its native state is greatly stabilized by binding one copper and one zinc atom per monomer rendering the protein dimeric. Loss of copper extinguishes dismutase activity and destabilizes the protein, increasing accessibility of the disulfide with monomerization accompanying disulfide reduction. A further pair of free thiols exist at C6 and C111 distant from metal binding sites, raising the question of their function. Here we investigate their role in misfolding of SOD1 along a pathway that leads to formation of amyloid fibrils. We present the seeding reaction of a mutant SOD1 lacking free sulfhydryl groups (AS-SOD1) to exclude variables caused by these free cysteines. Completely reduced fib"],"journal":["Frontiers in neuroscience"],"pubmed_title":["A Novel SOD1 Intermediate Oligomer, Role of Free Thiols and Disulfide Exchange."],"pmcid":["PMC7930385"],"funding_grant_id":["P01 NS049134"],"pubmed_authors":["Koo BK","Gralla EB","Munroe W","Whitelegge JP","Valentine JS"],"additional_accession":[]},"is_claimable":false,"name":"A Novel SOD1 Intermediate Oligomer, Role of Free Thiols and Disulfide Exchange.","description":"Wild-type human SOD1 forms a highly conserved intra-molecular disulfide bond between C57-C146, and in its native state is greatly stabilized by binding one copper and one zinc atom per monomer rendering the protein dimeric. Loss of copper extinguishes dismutase activity and destabilizes the protein, increasing accessibility of the disulfide with monomerization accompanying disulfide reduction. A further pair of free thiols exist at C6 and C111 distant from metal binding sites, raising the question of their function. Here we investigate their role in misfolding of SOD1 along a pathway that leads to formation of amyloid fibrils. We present the seeding reaction of a mutant SOD1 lacking free sulfhydryl groups (AS-SOD1) to exclude variables caused by these free cysteines. Completely reduced fib","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020","modification":"2025-04-04T22:01:13.717Z","creation":"2025-04-04T22:01:13.717Z"},"accession":"S-EPMC7930385","cross_references":{"pubmed":["33679289"],"doi":["10.3389/fnins.2020.619279"]}}